RESUMEN
BACKGROUND: In definite Creutzfeldt-Jakob disease (CJD), morphological and immunohistochemical patterns are useful to identify molecular subtypes. Severe cerebellar pathology and hippocampal involvement helps to identify VV subtypes. The rare VV1 variant (<1%), more frequent in young individuals, is additionally characterized by the presence of ballooned neurones in affected areas. In 1985, Cartier et al. described a family cluster of three individuals with an ataxic CJD form, showing, in addition to severe cerebellar and hippocampal involvement, the presence of frequent Hirano bodies (HB) in CA1 pyramidal neurones. HB are frequently found in aged individuals with Alzheimer pathology although they are not a specific finding. AIMS AND METHODS: In this study, we evaluated the presence of HB in hippocampi of 54 genetically and molecularly characterized CJD cases, aiming to elucidate whether additional morphological features could be helpful to point to molecular subtypes. RESULTS: We identified nine cases (four VV1, one out of three MV2K, three out of six MV2K+2C and one MV carrying a 96-base pair insertion) with abundant, partly bizarre and clustered HB in CA1 sector, not observed in other subtypes. The presence of HB was independent of hippocampal involvement by the disease itself. CONCLUSIONS: Clusters of abundant HB might be found in rare CJD subtypes such as VV1, MV2K/MV2K+2C and some genetic cases. In addition to histopathological and PrP immunohistochemical deposition patterns, their presence might be a useful additional morphologic feature that could point to the molecular subtype, especially when genetic and/or Western blot analyses are not available.
Asunto(s)
Encéfalo/patología , Síndrome de Creutzfeldt-Jakob/clasificación , Síndrome de Creutzfeldt-Jakob/patología , Hipocampo/patología , Proteínas 14-3-3/líquido cefalorraquídeo , Adulto , Factores de Edad , Anciano , Western Blotting , Encéfalo/metabolismo , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/metabolismo , Femenino , Hipocampo/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Proteínas PrPSc/metabolismoRESUMEN
BACKGROUND The clinical outcome of glioblastoma (GBM) patients who receive radiotherapy alone or with chemotherapy is well established. However, little is known about how many patients do not receive this treatment. We consider it is important to investigate why a proportion of operated patients do not receive further treatment after surgery. METHODS We reviewed all consecutive GBM patients operated on in our hospital between January 2000 and December 2008. RESULTS A total of 216 patients with GBM were identified. Fifty-five (25%) did not receive any treatment after surgery. Univariate analysis showed that factors associated with no further treatment after surgery were older than 60 years (p=0.002), of female gender (p=0.03), had a KPS<70 (p<0.001) and had had a biopsy (p<0.001). Multivariate analysis indicated that age =60 years and KPS <70 were independent predictors of no further treatment after surgery. Gender was not an independent variable. However, women in the whole series were older than 60 years (p=0.01), and they had a worse KPS (p=0.02) and more biopsies (p=0.04) than men. In the whole group, median survival time was 10.4 months for men (n=125) vs. 7.2 months for women (n=91), log rank p<0.04. This difference was not observed in the group that was treated after surgery. CONCLUSIONS One out of four patients could not be treated after surgery. Independent predictors were older age and low KPS. These poor risk variables were more frequent in women and their survival was therefore lower than men in our series.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/terapia , Glioblastoma/mortalidad , Glioblastoma/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/cirugía , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Glioblastoma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Radioterapia Adyuvante , Factores Sexuales , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenAsunto(s)
Autoanticuerpos/sangre , Glutamato Descarboxilasa/inmunología , Tumores Neuroendocrinos/diagnóstico , Degeneración Cerebelosa Paraneoplásica/diagnóstico , Neoplasias del Timo/diagnóstico , Terapia Combinada , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/inmunología , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/terapia , Examen Neurológico , Degeneración Cerebelosa Paraneoplásica/inmunología , Degeneración Cerebelosa Paraneoplásica/patología , Degeneración Cerebelosa Paraneoplásica/terapia , Timectomía , Timo/inmunología , Timo/patología , Neoplasias del Timo/inmunología , Neoplasias del Timo/patología , Neoplasias del Timo/terapiaRESUMEN
OBJECTIVE: To report the frequency and type of antibodies against neuronal surface antigens (NSA-ab) in limbic encephalitis (LE). METHODS: Analysis of clinical features, neuropathologic findings, and detection of NSA-ab using immunochemistry on rat tissue and neuronal cultures in a series of 45 patients with paraneoplastic (23) or idiopathic (22) LE. RESULTS: NSA-ab were identified in 29 patients (64%; 12 paraneoplastic, 17 idiopathic). Thirteen patients had voltage-gated potassium channels (VGKC)-ab, 11 novel NSA (nNSA)-ab, and 5 NMDA receptor (NMDAR)-ab. nNSA-ab did not identify a common antigen and were more frequent in paraneoplastic than idiopathic LE (39% vs 9%; p = 0.03). When compared with VGKC-ab or NMDAR-ab, the nNSA associated more frequently with intraneuronal antibodies (11% vs 73%; p = 0.001). Of 12 patients (9 nNSA-ab, 2 VGKC-ab, 1 NMDAR-ab) with paraneoplastic LE and NSA-ab, concomitant intraneuronal antibodies occurred in 9 (75%). None of these 12 patients improved with immunotherapy. The autopsy of three of them showed neuronal loss, microgliosis, and cytotoxic T cell infiltrates in the hippocampus and amygdala. These findings were compatible with a T-cell mediated neuronal damage. In contrast, 13 of 17 (76%) patients with idiopathic LE and NSA-ab (8 VGKC-ab, 4 NMDAR-ab, 1 nNSA-ab) and 1 of 5 (20%) without antibodies had clinical improvement (p = 0.04). CONCLUSIONS: In paraneoplastic limbic encephalitis (LE), novel antibodies against neuronal surface antigens (nNSA-ab) occur frequently, coexist with antibodies against intracellular antigens, and these cases are refractory to immunotherapy. In idiopathic LE, the likelihood of improvement is significantly higher in patients with NSA-ab than in those without antibodies.
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Anticuerpos/sangre , Antígenos de Superficie/inmunología , Encefalitis Límbica/inmunología , Encefalitis Límbica/patología , Neuronas/inmunología , Síndromes Paraneoplásicos/inmunología , Anciano , Anciano de 80 o más Años , Animales , Anticuerpos/análisis , Encéfalo/inmunología , Encéfalo/patología , Células Cultivadas , Femenino , Humanos , Inmunohistoquímica , Inmunoterapia , Encefalitis Límbica/mortalidad , Encefalitis Límbica/terapia , Masculino , Persona de Mediana Edad , Ratas , Resultado del TratamientoRESUMEN
We present one patient with Parry Romberg syndrome and another with linear scleroderma in coup de sabre, with focal neurologic deficits and intractable seizures arising from the hemisphere ipsilateral to the cutaneous lesion. Brain MRI showed progressive hemispheric atrophy. Pathology after functional hemispherectomy showed chronic inflammatory features suggestive of Rasmussen encephalitis.
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Encefalitis/complicaciones , Epilepsia/complicaciones , Hemiatrofia Facial/complicaciones , Esclerodermia Limitada/complicaciones , Telencéfalo/fisiopatología , Adulto , Edad de Inicio , Atrofia/inmunología , Atrofia/patología , Atrofia/fisiopatología , Enfermedades Autoinmunes/fisiopatología , Niño , Encefalitis/inmunología , Encefalitis/fisiopatología , Epilepsias Parciales/complicaciones , Epilepsias Parciales/inmunología , Epilepsias Parciales/fisiopatología , Epilepsia/inmunología , Epilepsia/fisiopatología , Hemiatrofia Facial/inmunología , Hemiatrofia Facial/fisiopatología , Femenino , Hemisferectomía , Humanos , Inmunosupresores/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Esclerodermia Limitada/inmunología , Esclerodermia Limitada/fisiopatología , Telencéfalo/inmunología , Telencéfalo/patología , Resultado del TratamientoRESUMEN
Extensive forest fires occurred in Catalonia, northern Spain, in 1994. In our study, concentrations and profiles of 12 parent polycyclic aromatic hydrocarbons (PAHs) were determined in riverine waters, ash and sediment samples at nine sampling sites (W1-W9) and at three sampling dates from Llobregat hydrographic basin: in August, 1994, one month after the extensive forest fires; in September, 1994, after the first heavy autumn rainfalls and in January, 1995, six months after forest fires. In August 1994, the total concentrations of 12 PAHs measured in riverine waters varied from 2 ng/l to 336 ng/l. In September 1994, the total PAH concentrations decreased to 0.2-31 ng/l and in January 1995, from 9 ng/l to 73 ng/l. In August, the composition pattern of PAHs showed a distribution dominated by 4-ring PAHs (pyrene, chrysene+triphenylene, benzo(a)anthracene) at W3-W6, W8 and W9 and 3-ring PAHs (phenanthrene) at W1, W2 and W7. In September, a preference by 3-ring PAHs (phenanthrene) at all sampling sites except W5 was shown and in January was clearly dominated by 4-ring PAHs (chrysene+triphenylene, pyrene, benzo(a)anthracene) at all sampling sites. In ash and sediment samples, the total concentrations of 12 PAHs ranged from 1.3 ng/g to 19 ng/g. The dominant compound was phenanthrene.
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Incendios , Sedimentos Geológicos/química , Hidrocarburos Policíclicos Aromáticos/análisis , Ríos/química , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , Lluvia , España , Árboles , Abastecimiento de AguaRESUMEN
UNLABELLED: The presence of neuronal intranuclear inclusions (NIIs) and neuronal mosaicism has been described in some autosomal dominant spinocerebellar ataxias (SCA), but their implication in neurodegenerative mechanisms still remains unclear. OBJECTIVE: To investigate the correlation between neuronal loss and NIIs, and the size of CAG triplet expansion in selected areas of the CNS in two SCA3 patients. MATERIAL AND METHODS: Postmortem neuropathological study was carried out, and the regional distribution of neuronal loss was compared with NIIs. CAG expansion was analysed by PCR amplification in the same regions. RESULTS: Marked neuronal loss was seen in the anterior horn of the spinal cord, pontine nuclei and motor nuclei of the brain stem. Moderate neurone loss was found in the locus ceruleus, colliculus and substantia nigra. Loss of granule and Purkinje cells was found in the cerebellum, mainly in the vermis. NIIs were present in neurones of the involved nuclei of the anterior horn of the spinal cord, medulla oblongata and pons, but not in the locus ceruleus, substantia nigra and cerebellum. A few NIIs were found in the striatum. The number of CAG repeats was 27/70 in the first patient and 21/74 in the second patient. The variation of the expanded allele size among different cerebral areas was +/-1-3 CAG repeats. CONCLUSION: The partial correlation between neuronal loss and NIIs suggests that other factors distinct from NII formation may be involved in the neuronal death. Moreover, the low degree of mosaicism between regions without neuronal loss and regions with marked neuronal loss points to the existence of selective cellular vulnerability to the genetic defect.
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Núcleo Celular/patología , Cuerpos de Inclusión/patología , Enfermedad de Machado-Joseph/patología , Mosaicismo/patología , Neuronas/patología , Repeticiones de Trinucleótidos/genética , Anciano , Anciano de 80 o más Años , Atrofia , Encéfalo/patología , Muerte Celular/genética , Núcleo Celular/genética , Femenino , Humanos , Cuerpos de Inclusión/genética , Enfermedad de Machado-Joseph/genética , Persona de Mediana Edad , Mosaicismo/genética , LinajeRESUMEN
We reviewed 200 patients with paraneoplastic encephalomyelitis (PEM) and anti-Hu antibodies to show possible clinical differences with respect to previous series, and to identify patient, tumour and treatment-related characteristics associated with neurological disability and survival. The median age of the 200 patients was 63 years (range 28-82 years) and 75% were men. The predominant neurological syndromes were sensory neuropathy (54%), cerebellar ataxia (10%), limbic encephalitis (9%) and multifocal involvement (11%). Sensorimotor neuropathies with predominant motor involvement were observed in only 4% of the patients. Pathological or X-ray evidence of a tumour was obtained in 167 patients (83%) and was a small-cell lung cancer (SCLC) in 74% of those with histological diagnosis. Coexistence of extrathoracic tumours with SCLC was rare (0.5%). Positive Hu immunoreactivity was observed in the extrathoracic tumours of six out of seven patients in whom autopsy or long-term follow-up ruled out a coexisting SCLC. PEM preceded the diagnosis of the tumour in 71% of patients (mean delay +/- SD 6.5 +/- 7.0 months; range 0.1-47 months). In the 24 patients in whom the tumour diagnosis was the initial event, PEM predicted the progression or relapse of the tumour in 87% of them. No tumour was found in 33 patients, including four who had a post-mortem study and four with >5 years of follow-up. In a logistic regression analysis, treatment of the tumour, associated or not with immunotherapy, was an independent predictor of improvement/stabilization of PEM [odds ratio 4.56; 95% confidence interval (CI) 1.62-12.86]. Cox multivariate analysis indicated that the variables independently associated with mortality were: age >60 years [relative risk (RR) 1.49; 95% CI 1.05-2.12], Rankin score at diagnosis >3 (RR 1.60; 95% CI 1.12-2.28), more than one area of the nervous system affected (RR 1.61; 95% CI 1.08-2.40), and absence of treatment (RR 2.56; 95% CI 1.76-3.71). We conclude that, unlike previous series, the majority of our patients were male, and there was a low occurrence of predominantly motor neuropathies and extrathoracic tumours coexisting with SCLC. When the diagnosed extrathoracic tumour expresses Hu antigens, further tests to rule out a coexisting SCLC are probably unnecessary. Finally, the predictors of mortality and PEM evolution found in the study may be important in the design of future therapeutic protocols, and emphasize the importance of early diagnosis and treatment of the underlying tumour.
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Anticuerpos/sangre , Neoplasias/complicaciones , Proteínas del Tejido Nervioso/sangre , Sistema Nervioso/fisiopatología , Síndromes Paraneoplásicos del Sistema Nervioso/patología , Síndromes Paraneoplásicos del Sistema Nervioso/fisiopatología , Proteínas de Unión al ARN/sangre , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos/inmunología , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Pequeñas/complicaciones , Carcinoma de Células Pequeñas/inmunología , Carcinoma de Células Pequeñas/fisiopatología , Proteínas ELAV , Femenino , Humanos , Inmunoterapia , Masculino , Persona de Mediana Edad , Neoplasias/inmunología , Neoplasias/patología , Proteínas del Tejido Nervioso/inmunología , Sistema Nervioso/inmunología , Sistema Nervioso/patología , Polineuropatía Paraneoplásica/inmunología , Polineuropatía Paraneoplásica/patología , Polineuropatía Paraneoplásica/fisiopatología , Síndromes Paraneoplásicos del Sistema Nervioso/inmunología , Proteínas de Unión al ARN/inmunología , Trastornos Somatosensoriales/inmunología , Trastornos Somatosensoriales/patología , Trastornos Somatosensoriales/fisiopatología , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Abnormal tau phosphorylation and deposition in neurones and glial cells is one of the major features in taupathies. The present study examines the involvement of the Ras/MEK/ERK pathway of tau phosphorylation in Alzheimer disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), by Western blotting, single and double-labelling immunohistochemistry, and p21Ras activation assay. Since this pathway is also activated in several paradigms of cell death and cell survival, activated ERK expression is also analysed with double-labelling immunohistochemistry and in situ end-labelling of nuclear DNA fragmentation to visualise activated ERK in cells with increased nuclear DNA vulnerability. The MEK1 antibody recognises one band of 45 kD that identifies phosphorylation-independent MEK1, whose expression levels are not modified in diseased brains. The ERK antibody recognises one band of 42 kD corresponding to the molecular weight of phosphorylation-independent ERK2; the expression levels, as well as the immunoreactivity of ERK in individual cells, is not changed in AD, PiD, PSP and CBD. The antibody MAPK-P distinguishes two bands of 44 kD and 42 kD that detect phosphorylated ERK1 and ERK2. MAPK-P expression levels, as seen with Western blotting, are markedly increased in AD, PiD, PSP and CBD. Moreover, immunohistochemistry discloses granular precipitates in the cytoplasm of neurones in AD, mainly in a subpopulation of neurones exhibiting early tau deposition, whereas neurones with developed neurofibrillary tangles are less commonly immunostained. MAPK-P also decorates neurones with Pick bodies in PiD, early tau deposition in neurones in PSP and CBD, and cortical achromatic neurones in CBD. In addition, strong MAPK-P immunoreactivity is found in large numbers of tau-positive glial cells in PSP and CBD, as seen with double-labelling immunohistochemistry. Yet no co-localisation of enhanced phosphorylated ERK immunoreactivity and nuclear DNA fragmentation is found in AD, PiD, PSP and CBD. Finally, activated Ras expression levels are increased in AD cases when compared with controls. These results demonstrate increased phosphorylated (active) ERK expression in association with early tau deposition in neurones and glial cells in taupathies, and suggest activated Ras as the upstream activator of the MEK/ERK pathway of tau phosphorylation in AD.
Asunto(s)
Enfermedad de Alzheimer/patología , Enfermedades de los Ganglios Basales/patología , Núcleo Celular/metabolismo , ADN/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neuroglía/patología , Neuronas/patología , Enfermedad de Pick/patología , Parálisis Supranuclear Progresiva/patología , Proteínas tau/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Enfermedades de los Ganglios Basales/metabolismo , Muerte Celular , Núcleo Celular/patología , Corteza Cerebral/patología , Fragmentación del ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteína Quinasa 3 Activada por Mitógenos , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/patología , Neuroglía/metabolismo , Neuronas/metabolismo , Fosforilación , Enfermedad de Pick/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Parálisis Supranuclear Progresiva/metabolismoRESUMEN
Prion protein (PrPC) is a glycolipid-anchored cell membrane sialoglycoprotein that localises in presynaptic membranes. Since synapses are vulnerable to Alzheimer's disease (AD), the present study examines PrPC expression in senile plaques, one of the major structural abnormalities in AD, by single- and double-labelling immunohistochemistry. Punctate PrPC immunoreactivity is found in diffuse plaques, whereas isolated large coarse PrPC-positive granules reminiscent of dystrophic neurites are observed in neuritic plaques. Finally, PrPC deposition also occurs as dense filamentous and amorphous precipitates in amyloid cores of senile plaques, but not in the walls of blood vessels with amyloid angiopathy. In contrast to PrPC, betaA4-amyloid immunoreactivity is preserved and even enhanced following incubation of the tissue sections with proteinase K prior to immunohistochemistry, thus indicating no PrPC and betaA4-amyloid cross-reactivity in dense amyloid cores of senile plaques. Punctate PrPC deposition in diffuse plaques is similar to that of synaptophysin, a synaptic vesicle-associated protein, as already reported in other studies. Immunoprecipitation, electrophoresis and Western blot studies have shown that synaptophysin, amyloid precursor protein (APP) and betaA4 do not co-precipitate with PrP. These results suggest that synaptophysin, APP and betaA4 are likely not bound to PrP. PrPC accumulation in betaA4-amyloid dense cores may be the consequence of the release of PrP into the extracellular space. Whether PrPC accumulation in the extracellular space is the result of impaired endocytosis and subsequent hydrolysis in the endosomal compartment, in contrast to normal degradation of PrPC, resulting from or occurring in parallel to abnormal APP degradation, deserves further study.
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Enfermedad de Alzheimer/patología , Hipocampo/patología , Placa Amiloide/patología , Proteínas PrPC/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/fisiopatología , Péptidos beta-Amiloides/metabolismo , Femenino , Hipocampo/fisiopatología , Humanos , Masculino , Sinaptofisina/metabolismoRESUMEN
Drawbacks of hepatitis C virus (HCV) RNA detection in paraffin-embedded liver tissue have satisfactorily been solved by RT-PCR amplification of the 5'non-coding region (5'NCR). However, detection of this highly conserved region does not provide information on epidemiological or pathogenetic aspects of HCV infection. This study explores whether other functionally important genetic regions of HCV, such as the hypervariable region 1 (HVR-1) and the interferon sensitivity-determining region (ISDR), can be retrieved from paraffin-embedded liver specimens by RT-PCR, and whether the amplified material is suitable for further molecular analyses. RT-PCR amplification of 5'NCR, HVR-1, and ISDR was assessed in RNA extracted from 50 formalin-fixed, paraffin-embedded liver specimens, including 23 needle liver biopsies (11 from patients with non-A, non-B chronic hepatitis diagnosed between 1971 and 1985, 8 from subjects with normal liver histology and 4 from sequential biopsies from a patient with HCV recurrence after liver transplantation), and 27 liver explants from patients undergoing transplantation between 1988 and 1996 (16 with HCV-related cirrhosis and 11 with other disorders). The 5'NCR was successfully amplified in 8 of 11 (73%) non-A, non-B chronic hepatitis biopsies and in all of the specimens from patients with serological documentation of HCV infection. There were no false-positive results. HCV genotype was identified by RFLP analysis of the 5'NCR in the 13 cases analyzed. HVR-1 and ISDR were amplified in 24 of 28 (86%) samples, which were positive for the 5'NCR. Efficient amplification was inversely related to the time of storage. The evolutionary changes of HVR-1 and ISDR were successfully analyzed by direct sequencing of amplificates from the explanted liver and from the sequential liver biopsies in a patient with HCV infection recurrence after transplantation. These observations indicate that paraffin-embedded liver tissue, even when stored for more than 20 years, is appropriate for advanced studies on the molecular biology of HCV.
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Evolución Molecular , Hepacivirus/genética , Hepatitis C Crónica/patología , Hígado/virología , Polimorfismo de Longitud del Fragmento de Restricción , Secuencia de Aminoácidos , Biopsia con Aguja , Formaldehído , Amplificación de Genes , Variación Genética , Genoma Viral , Genotipo , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/virología , Humanos , Hígado/patología , Datos de Secuencia Molecular , Parafina , ARN Viral/aislamiento & purificación , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adhesión del TejidoRESUMEN
Electron microscopy (EM) is a valuable standard tool in basic research and teaching. However, its use in diagnosis is limited, either for strategic reasons or budgetary constraints. This means that its many potential applications are more often neglected, either as an ancillary tool, quality control method, or gold standard, to complement, support, or confirm results of pathological studies. To evaluate the use of EM in this setting, the authors analyzed all articles (n = 2,531) in the three top indexed diagnostic pathology journals for a period of 60 months from July 1993 to June 1998. A total of 448 articles in which the use of EM was indicated, according to standard surgical pathology textbooks, were selected. Both the actual and the potential EM content of each article were scored, as follows: zero, illustrative, supportive, gold standard (for confirmation of research results), extensive, and predominant. Of the total number of articles in which EM was indicated, 77% made use of the technique. EM support was lacking most frequently in articles on serosal neoplasms and on new diagnostic strategies (p < .00005). There was no definite trend toward an increase or decrease in the use of EM during the period analyzed. The authors conclude that EM is used in most reports on diagnostic pathology, when it is indicated. However, a small but non-negligible percentage of articles (23%) could benefit from including EM as an ancillary, control, or gold standard method to complement, support, or confirm their results.
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Microscopía Electrónica/estadística & datos numéricos , Microscopía Electrónica/tendencias , Patología Clínica/tendencias , Diagnóstico Diferencial , Femenino , Enfermedades Urogenitales Femeninas/diagnóstico , Enfermedades Urogenitales Femeninas/patología , Enfermedades de los Genitales Femeninos/diagnóstico , Enfermedades de los Genitales Femeninos/patología , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/patología , Humanos , Periodismo Médico , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/patología , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/patología , Patología Clínica/instrumentación , Publicaciones Periódicas como Asunto/estadística & datos numéricos , Publicaciones Periódicas como Asunto/tendencias , Estudios Retrospectivos , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/ultraestructuraRESUMEN
Trophic factors, administered systemically or delivered via genetically-modified cells grafted into target regions, have been proposed as putative therapeutic agents in human neurodegenerative disorders. In parallel to the study of the beneficial effects in experimental models of particular diseases, a crucial aspect of the study of trophic factors is the gathering of information about the actual trophic factor expression in human diseased states. Brain-derived neurotrophic factor (BDNF) promotes survival and growth of various nerve cell populations during normal development and following various insults in the developing and adult brain. In particular, BDNF prevents cell death of certain striatal populations in excitotoxic models of Huntington disease (HD) following intrastriatal injection of quinolinic acid to the adult rodent brain. The present study examines BDNF expression, by gel electrophoresis and Western blotting, and immunohistochemistry, in the brains of patients who had suffered from HD. Reduced BDNF expression, ranging from 53 to 82%, has been found in the caudate and putamen in HD when compared with age-matched controls. No modifications in BDNF expression levels have been seen in the parietal cortex, temporal cortex and hippocampus. Furthermore, immunohistochemistry has shown reduced BDNF immunoreactivity in caudate neurons, but not in cortical neurons in HD when compared with controls. These data demonstrate selective BDNF decay in regions that are vulnerable to HD, and suggest, in combination with results in experimental models, that a BDNF surplus may have beneficial effects in the treatment of HD.
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Factor Neurotrófico Derivado del Encéfalo/deficiencia , Enfermedad de Huntington/metabolismo , Anciano , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/fisiopatología , Femenino , Humanos , Enfermedad de Huntington/patología , Enfermedad de Huntington/fisiopatología , Masculino , Neuronas/metabolismo , Neuronas/patologíaRESUMEN
A 73-year-old woman presented with an hemorrhagic kidney tumor initially interpreted as a renal cell carcinoma (RCC). A retroperitoneal recurrence infiltrating the duodenal wall was made up of clear cells, some of which contained Fontana-Masson positive pigment, immunopositive for HMB-45, S-100 protein, actin, and vimentin. The same immunohistochemical profile was retrospectively reproduced in the kidney tumor, where melanosomes were also found ultrastructurally. Lipomatous differentiation was not observed. There was no history of malignant melanoma (MM), or stigmata of tuberous sclerosis. The patient died of disease 5 years after the initial diagnosis. This neoplasm can be considered as a malignant, pigmented, clear-cell epithelioid variant of angiomyolipoma, or "sugar" tumor of the kidney, with the peculiarity of having a previously unreported component of pigmented cells visible on light microscopy. This finding raises the possibility that the exceptional cases of MM reported in renal parenchyma may be pigmented variants of epithelioid angiomyolipoma rather than true MM.
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Angiomiolipoma/diagnóstico , Neoplasias Renales/diagnóstico , Melanoma/diagnóstico , Anciano , Angiomiolipoma/química , Angiomiolipoma/cirugía , Biomarcadores de Tumor/análisis , Carcinoma de Células Renales/diagnóstico , Diagnóstico Diferencial , Resultado Fatal , Femenino , Humanos , Técnicas para Inmunoenzimas , Neoplasias Renales/química , Neoplasias Renales/cirugía , Melanoma/química , Melanoma/cirugía , Melanosomas/ultraestructura , Recurrencia Local de Neoplasia/patologíaRESUMEN
Brain-derived neurotrophic factor (BDNF) promotes survival and growth of various nerve cell populations during normal development and following different insults in the developing and adult brain. BDNF expression is reduced in Alzheimer disease, but little is known about BDNF expression in other types of dementia. Frontotemporal dementia (FTD) is a common cause of mental impairment in old age, which is characterized by neuron loss in the upper cortical layers mainly of the frontal and temporal cortex. BDNF protein expression has been examined by Western blotting and immunohistochemistry in the cerebral cortex of individuals affected by FTD. Examination of pathological samples (n = 8, mean age: 74.7 years; four men, four women) was conducted in parallel with corresponding samples from age-matched controls (n = 8; mean age: 72.6 years; three men, five women). Post-mortem delay was between 2 and 6 h. Preserved BDNF expression, as revealed by Western blotting, has been observed in the frontal and temporal cortices of patients with FTD. Furthermore, immunohistochemistry has disclosed maintained BDNF immunoreactivity in surviving neurons of the upper cellular layers, as well as in neurons of the inner cellular layers in FTD. These results show that FTD is not associated with a decay of BDNF in cortical neurons, and therefore, that BDNF is differentially regulated in diseases causing dementia.
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Factor Neurotrófico Derivado del Encéfalo/análisis , Demencia/fisiopatología , Lóbulo Frontal/fisiopatología , Lóbulo Temporal/fisiopatología , Anciano , Anciano de 80 o más Años , Femenino , Lóbulo Frontal/patología , Humanos , Masculino , Neuronas/metabolismo , Neuronas/patología , Lóbulo Temporal/patologíaAsunto(s)
Ataxia/etiología , Neoplasias Encefálicas/complicaciones , Confusión/etiología , Linfoma de Células B/complicaciones , Linfoma de Células B Grandes Difuso/complicaciones , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patología , Diagnóstico Diferencial , Femenino , Humanos , Linfoma de Células B/diagnóstico , Linfoma de Células B/patología , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/patología , Imagen por Resonancia Magnética , Persona de Mediana Edad , Síndrome , Tomografía Computarizada por Rayos XAsunto(s)
Aneurisma/enzimología , Aneurisma/etiología , Trasplante de Riñón , Elastasa de Leucocito/sangre , Deficiencia de alfa 1-Antitripsina/complicaciones , Aneurisma/sangre , Aneurisma/diagnóstico por imagen , Angiografía de Substracción Digital , Arteria Braquial/diagnóstico por imagen , Arteria Braquial/patología , Humanos , Masculino , Persona de Mediana Edad , Arteria Esplénica/diagnóstico por imagen , Arteria Esplénica/patología , Deficiencia de alfa 1-Antitripsina/sangreRESUMEN
Brain-derived neurotrophic factor (BDNF), and full-length and truncated tyrosin kinase B receptor (TrkB) protein expression were examined by Western blotting and immunohistochemistry in the frontal cortex and hippocampus of individuals affected by long-lasting severe Alzheimer disease (AD) and age-matched controls. Since preliminary processing studies in the brains of rats have shown loss of immunoreactivity depending on the postmortem delay in tissue processing and on the type, duration, and temperature of the fixative solution, only human samples obtained up to 6 hours (h) after death for biochemical and morphological studies and fixed by immersion in 4% paraformaldehyde for 24 h for morphological studies were included in the present series. Decreased BDNF and full-length TrkB expression accompanied by increased truncated TrkB expression, as revealed by Western blotting, was observed in the frontal cortex of patients with AD. Immunohistochemistry disclosed reduced BDNF and full-length TrkB immunoreactivity in neurons. BDNF decrease was equally observed in tangle-bearing and non-tangle-bearing neurons, as revealed with double-labeling immunohistochemistry to BDNF and phosphorylated tau or phosphorylated neurofilament epitopes. Full-length TrkB immunoreactivity was largely decreased in tangle-bearing neurons, whereas only moderate decreases occurred in neurons with granulovacuolar degeneration. Strong BDNF immunoreactivity was observed in dystrophic neurites surrounding senile plaques, whereas strong TrkB expression occurred in reactive glial cells, including those surrounding senile plaques. Finally, truncated TrkB immunoreactivity was observed in individual neurons and in reactive glial cells in the cerebral cortex and white matter in AD. These results show decay in the expression of BDNF and TrkB in AD neurons, accompanied by altered BDNF, and full-length and truncated TrkB expression in dystrophic neurites and reactive glial cells, respectively, in this disease. The present results demonstrate selective decline of the BDNF/TrkB neurotrophic signaling pathway in the frontal cortex and hippocampus in AD and provide supplemental data that may be relevant in discussing the suitability of the use of BDNF as a therapeutic agent in patients with AD.
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Enfermedad de Alzheimer/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptores de Factor de Crecimiento Nervioso/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/terapia , Femenino , Lóbulo Frontal/metabolismo , Hipocampo/metabolismo , Técnicas Histológicas , Humanos , Masculino , Fragmentos de Péptidos/metabolismo , Cambios Post Mortem , Proteínas Tirosina Quinasas Receptoras/química , Receptor de Factor Neurotrófico Ciliar , Receptores de Factor de Crecimiento Nervioso/químicaRESUMEN
The finding of conduction block (CB) within short consecutive segments along a motor nerve is a key feature of multifocal motor neuropathy (MMN). Despite their different pathogenesis, this may be the only clinical difference between some cases of MMN and the pure spinal muscular atrophy form of motor neuron disease (MND). In 12 patients with distal atrophy and fasciculations and electrophysiological evidence of CBs in the upper limbs, we measured the peripheral and central motor conduction times (PMCT and CMCT) to hand muscles. We reasoned that patients with MMN should show an abnormally prolonged PMCT with normal CMCT, whereas an increased CMCT would suggest MND. All patients had delayed F-wave latency and increased PMCT. Three patients had increased CMCT. Follow-up showed little clinical and electrophysiological change in 7 of the 9 patients with normal CMCT, and a progressive motor deficit leading ultimately to death in 1 of the 3 patients with increased CMCT. This patient's electrophysiological follow-up showed a significant decrement of the compound motor action potential to both proximal and distal stimulation points, with disappearance of earlier CBs. Autopsy revealed loss of anterior horn cells and axons of the ventral root, and degeneration of large myelinated fibers. We conclude that determining the CMCT may help in differentiating MND from MMN. Persistence of a stable clinical picture over a span of at least 1 year and lack of electrophysiological signs of involvement of upper motor neurons should both be required before establishing the diagnosis of MMN even with electrophysiological evidence of CB.
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Enfermedades del Sistema Nervioso Central/fisiopatología , Enfermedad de la Neurona Motora/fisiopatología , Bloqueo Nervioso , Conducción Nerviosa , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A case of retroperitoneal fibrosis with an unusual perirenal involvement diagnosed at MR imaging is reported. Other conditions, such as metastatic disease or lymphoma, may be considered especially when the initial presentation is not typical. Imaging modalities in this condition are discussed.